Invoked — ironically, by a villain — in Hercules. Hades poses this hypothetical question to his lackeys Pain and Panic: How do you kill a god? Pain and Panic, playing along, remark that this is impossible, since gods are immortal. Hades then explains to them his plan to use his dark magic to turn the baby Hercules into a human just so he can be killed.
Monkey manages to kill the first Sister in single combat. While she's actually Kubo's mother, she seems to have none of her powers and does so in melee combat.
Kubo manages to kill the second Sister with a shockwave of Magic Music, though Beetle had wounded her beforehand.
Kubo ultimately defeats the Moon King with The Power of Love, turning him into a human without any memories.
In the climax of The Little Mermaid (1989), Prince Eric (a normal man) is up against Ursula after she just went One-Winged Angel after gaining Triton's trident and now controls the entire ocean. To save Ariel, Eric rams a ship into Ursula, impaling and killing her with the bowsprit.
A minor one in Meet the Robinsons; Wilbur manages to take down a T Rex (like what) with only a meatball cannon.
In Turning Red, Mei resorts to headbutting her giant red panda mother to stop her rampaging in the 4*Town concert. She's not happy about it, though.
The Twelve Tasks of Asterix has Asterix and Obelix going through a "Cave of the Beast", a fearsome creature no one met and returned to tell the tale. We never see it, but in the scene after the Gauls leave the cave...
Caius Tiddlus: Pardon my curiosity, but what was is the Beast like? Obelix:Very tasty! Waiter! I'd like a drink!
Wonder Woman and Superman being able to overpower Doomsday count as this, though it takes a Heroic Sacrifice from Superman using a Kryptonite Spear to kill Doomsday.
Conan the Destroyer: What to do when you involuntarily helped the return of an ancient monstrous god? Wrestle him and rip off his horn with your bare hands, of course!
Constantine. It's not Hellblazer, but the ending is true to the series lore. John thwarts Mammon, out-foxes the Devil, gets the archangel Gabriel stripped of their power and booted from Heaven...then greets them with a haymaker. "That's called pain. Get used to it. Welcome to mortality, Gabs."
In Dogma, when Silent Bob kills the demon Azrael with Cardinal Glick's driver. Granted, the clubs in question were blessed by a priest (because the priest would be the kind of guy to do that), but when mortals are taking out demons you can't be picky about the methodology..
In End of Days, Schwarzenegger is an alcoholic gumshoe who does battle with Lucifer, throwing him out a window and even blasting him with an RPG at one point. Eventually his human vessel gets too banged-up to fix, so the Devil takes over Arnold's body. The old body was specifically cultivated for the Devil to inhabit, but Arnold is an unknown quantity and can't be controlled as easily, so Arnold wins. The movie is a little too self-serious for action fans to enjoy (horror doesn't really play to Arnold's strengths) and is routinely cited as one of his top 3 worst films. Still, it has some nice moments of Arnold turning into a rage monster.
"The Man": Now you're upsetting me. You don't want to see me upset, believe me. Jericho: Oh, you want to fuck with me? You think you know bad, huh? You're a fucking CHOIR BOY compared to me! A CHOIR BOY!!
Ghostbusters (1984): The eponymous busters have to Cross The Streams to do it, but they defeat Gozer the Gozerian, an ancient god worshipped by the Hittites, Mesopotamians, and the Sumerians around 6000BC that would take on a Destructor Form from the thoughts of humans in the area and wreak havoc once it was summoned into their world. Their line about their first ghost-busting job which actually concerned Slimer, would feel much more fitting in this case.
We came, we saw, we kicked its ass!
Believe it or not, the Godzilla franchise has a few occasions where humanity actually succeeds at defeating the King of Monsters or another Kaiju:
The first instance happened in the original movie, when doctor Serizawa revealed the Oxygen Destroyer, the weapon that disintegrated the original Godzilla... And left Tokyo Bay completely devoid of life.
In Atragon the title ship (original name: Gohten) engages Manda, Mu's guardian dragon, and freezes it to the seabed.
In Godzilla: Final Wars the Gotengo makes her triumphant return by defeating Godzilla itself, though she was almost destroyed in the process and could only leave him frozen in the Arctic. Later in the movie, the upgraded Gotengo engages and kills Manda, and during the Xillian invasion they free Godzilla to fight the aliens.
In Shin Godzilla the JSDF, facing the perspective of the Americans nuking Tokyo to destroy the kaiju, literally drops everything they have on it (including freight trains and even buildings), eventually leaving the King of Monsters blocked with plenty of blood coagulants. Previously the Americans actually significantly damaged him with a pair of GBU-57s.
Godzilla Minus One features probably one of the most impressive examples of this considering how underpowered the human characters are, being war torn Japanese civilians and ex-vets up against a powerful more modern beam spamming Godzilla and unlike the original film don’t even have a super weapon like the Oxygen Destroyer. Nonetheless thanks to making use of Freon tanks, the crushing weight and decompression of the ocean and a kamikaze plane full of explosives they are able to put Goji down and have a ending where Everyone Lives. Though The Stinger infers Godzilla will eventually reform himself with his Healing Factor.
Hellboy (2004) features its titular demonic hero being swallowed by the tentacled God of Chaos. Fortunately, Hellboy is wearing a belt of grenades which he then detonates, blowing the creature up from the inside, leaving Hellboy remarkably unharmed.
It (2017): In the climactic battle, The Losers' Club beat up Pennywise and boot the native Eldritch Abomination back into hibernation.
Captain America stands up to Loki, the God of Mischief, deflecting his blast aimed for a defiant old man and going on to fight Loki hand-to-hand. Then there's Iron Man, who not only blasts Loki down twice but goes toe to toe with Thor and at multiple points actually tosses the God of Thunder around like a beachball. Hulk of course goes several steps further, subjecting both Thor and Loki respectively to a massive beatdown and even lampshading it with the latter.
Hulk: Puny God.
Hawkeye's moment where he shoots an arrow at Loki, who catches it with a withering expression on his face moments before the arrow detonates, blowing him into a building.
Badass Normal Agent Coulson who blows Loki through a wall with a BFG.
The Big Bad of Guardians of the Galaxy Vol. 2 proves to be Ego the Living Planet. Ultimately, he meets his fate at the hands of Rocket and Groot traveling to his brain deep underground, and planting a bomb powered by the Anulax Batteries Rocket had stolen earlier.
Thor gets this reaction from the population of Sakaar when he unlocks his true Shock and Awe powers and sends Hulk flying with one lightning-powered punch during the Gladiator Games.
Hulk actually goes so far as to punch out Surtur and briefly stuns him. Hulk is then tossed back to the bridge and needs to be coaxed to run away... right before Surtur completes his prophetic duty of destroying Asgard.
Thanos from Avengers: Infinity War who is seemingly just an ordinary but determined alien warlord, managed to curb-stomp both the gods Thor and Loki, even casually choking the latter to death after a failed attempt at backstabbing the Mad Titan.
More important was that with nothing but the Power Stone, Thanos punched the Hulk so badly the Hulk refused to fight for the entire film... Not Bruce Banner, who participated in the final battle... the Hulk... Bruce's attempts to transform into the Not So Jolly Green Giant were met with the Hulk's vocal protests. Keep in mind that Hulk's strength comes from his anger and as Tony and Thor both find out the hard way, punching Hulk is only going to make him angrier. Thanos was so powerful, he did the one thing you should never do when dealing with the Hulk, and left the Hulk terrified.
On the other hand during the film’s climax Thor, who Took a Level in Badass thanks to the power of Stormbreaker, throws his new toy so that it powers through a Combined Energy Attack from Thanos wielding all Six Infinity Stones and impales the Titan in the chest mortally wounding him. Thor would’ve ended the whole movie right there, had he aimed for the head.
Avengers: Endgame flips the script entirely on Thanos as Captain America (wielding Mjölnir), Scarlet Witch and Captain Marvel respectively succeed in kicking the Mad Titan's ass, Scarlet Witch in particular freaks him enough that he orders a Orbital Bombardment and sacrifices a significant number of his troops to get away from her. Wanda is only outdone by Iron Man who with a Badass Fingersnap turns Thanos and his entire army into dust.
Stacker Pentecost: I've never believed in the End Times. We are mankind. Our footprints are on the moon. When the last trumpet sounds and the Beast rises from the pit — we will kill it.
First, our protagonists manage to kill The Antichrist with several different guns and a shovel.
Then Ben manages to laser-fry Jesus before he can help fight the newly-reincarnated Satan.
Finally, God Himself comes down from Heaven, yells at our protagonists, and does battle with Satan...only for both of them to fall into a jacuzzi and get electrocuted by a stereo.
Subverted in Sin City where this very act is invoked (sarcastically) as a metaphor for doing something that is completely impossible.
Hartigan: And after I pull off that miracle, maybe I'll go punch out God.
Star Trek V: The Final Frontier has the God imposter blown up by a torpedo then vaporized by ship-mounted disruptors. Spock did it.
Suicide Squad (2016) has The Enchantress and her brother Incubus two extremely powerful and ancient Eldritch Abominations. The latter gets overpowered and killed by one meta-human with Playing with Fire powers. The former gets matched and then exploded by one army colonel, a guy who can shoot well, a guy with a boomerang, a crocodile man, a Japanese lady with a Cool Sword and Cute and Psycho former psychiatrist with a baseball bat.
In the climax of The Suicide Squad the B-Team take on Starro an Eldritch Abomination from outer space. King Shark aka Nanaue chomps Starro up, Polka-Dot Man blows Starro's leg off, but it all comes down to Harley Quinn breaking through Starro's eye with a javelin enabling Ratcatcher II to kill Starro with an army of rats, which crawl inside and chew up its brain.
There's also Bloodsport's backstory: he's a normal (albeit highly-trained) human who put Superman in the ICU by shooting him with a kryptonite bullet.
Underwater: Norah disables the safeguards for Roebuck Station, and causes a reactor meltdown to nuke what Word of God confirms is Cthulhu.
Wonder Woman (2017): The Opening Narration reveals War God Ares pulled a Kratos and killed the entire Greek Pantheon. Diana in the climax kills Ares herself thanks of a combination of her lightning absorbing bracelets and The Power of Love.
X-Men: Apocalypse: When Jean Grey accesses the full force of the Phoenix, she ultimately becomes the one who defeats Apocalypse, the first and most powerful mutant. Everything is a Curb-Stomp Battle for her.
During the climax as a non-verbal "Fuck You" to the Apokolips and Darkseid in particular, Aquaman stabs the New God Steppenwolf through the torso, Superman sends him flying and Wonder Woman beheads him just as he goes through the portal. Granted Superman had greatly softened Steppenwolf with a No-Holds-Barred Beatdown prior.
There's also the ancient invasion where Darkseid himself invaded looking for the Anti-Life Equation and got his ass kicked by the united forces of Greek Gods, Amazons, Atlanteans and regular human armies. Ares even critically wounded Darkseid with an axe to the shoulder.
but is in the movie as well.